Thymidylate synthase is a well-recognized target for anti-cancer, anti-fungal and anti-parasitic drugs. We have crystallized thymidylate synthase from the species Cryptococcus neoformans, Cryptosporidium parvum, Pneumocystis carinii and Toxoplasma gondii. We plan on doing structure-based drug design studies on all four species using anti-folate and lipophilic drug leads available in the laboratory.